Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial
Thierry André
(1, 2, 1)
,
Dewi Vernerey
(3, 4)
,
Laurent Mineur
(5)
,
Jaafar Bennouna
(6, 6)
,
Jérôme Desramé
(7)
,
Roger Faroux
(8)
,
Serge Fratte
(3, 9)
,
Marine Hug de Larauze
(1)
,
Sophie Paget-Bailly
(3)
,
Benoist Chibaudel
(1, 1)
,
Jérémie Bez
(10)
,
Jérôme Dauba
(11)
,
Christophe Louvet
(12)
,
Céline Lepère
(13)
,
Olivier Dupuis
(14)
,
Yves Bécouarn
(15)
,
May Mabro
(16)
,
J. Egreteau
(17)
,
Olivier Bouché
(18)
,
Gaël Deplanque
(19)
,
Marc Ychou
(20, 21)
,
Marie-Pierre Galais
(22)
,
François Ghiringhelli
(23)
,
Louis Marie Dourthe
(24)
,
Jean-Baptiste Bachet
(25, 2)
,
Ahmed Khalil
(26)
,
Franck Bonnetain
(4)
,
Aimery de Gramont
(27)
,
Julien Taieb
(13, 28, 29)
1
CHU Saint-Antoine [AP-HP]
2 SU - Sorbonne Université
3 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
4 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
5 Institut Sainte Catherine [Avignon]
6 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
7 Hôpital privé Jean Mermoz
8 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
9 CH Belfort-Montbéliard
10 Fédération Francophone de la Cancérologie Digestive, FFCD
11 Centre Hospitalier Layné
12 IMM - Institut Mutualiste de Montsouris
13 HEGP - Hôpital Européen Georges Pompidou [APHP]
14 Clinique Victor Hugo
15 Institut Bergonié [Bordeaux]
16 Hôpital Foch [Suresnes]
17 GHBS - Groupe Hospitalier Bretagne Sud
18 Hôpital universitaire Robert Debré [Reims]
19 hpsj - Groupe Hospitalier Paris Saint-Joseph
20 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
23 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
24 Clinique Sainte Anne [Strasbourg]
25 CHU Pitié-Salpêtrière [AP-HP]
26 CHU Tenon [AP-HP]
27 Institut hospitalier Franco-Britannique [Levallois-Perret]
28 USPC - Université Sorbonne Paris Cité
29 UPD5 - Université Paris Descartes - Paris 5
2 SU - Sorbonne Université
3 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
4 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
5 Institut Sainte Catherine [Avignon]
6 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
7 Hôpital privé Jean Mermoz
8 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
9 CH Belfort-Montbéliard
10 Fédération Francophone de la Cancérologie Digestive, FFCD
11 Centre Hospitalier Layné
12 IMM - Institut Mutualiste de Montsouris
13 HEGP - Hôpital Européen Georges Pompidou [APHP]
14 Clinique Victor Hugo
15 Institut Bergonié [Bordeaux]
16 Hôpital Foch [Suresnes]
17 GHBS - Groupe Hospitalier Bretagne Sud
18 Hôpital universitaire Robert Debré [Reims]
19 hpsj - Groupe Hospitalier Paris Saint-Joseph
20 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
23 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
24 Clinique Sainte Anne [Strasbourg]
25 CHU Pitié-Salpêtrière [AP-HP]
26 CHU Tenon [AP-HP]
27 Institut hospitalier Franco-Britannique [Levallois-Perret]
28 USPC - Université Sorbonne Paris Cité
29 UPD5 - Université Paris Descartes - Paris 5
Thierry André
- Fonction : Auteur
- PersonId : 761084
- ORCID : 0000-0002-7718-2645
Dewi Vernerey
- Fonction : Auteur
- PersonId : 773789
- IdRef : 199443882
Jaafar Bennouna
- Fonction : Auteur
- PersonId : 766590
- ORCID : 0000-0002-5034-1108
Serge Fratte
- Fonction : Auteur
- PersonId : 950315
Sophie Paget-Bailly
- Fonction : Auteur
- PersonId : 1014980
François Ghiringhelli
- Fonction : Auteur
- PersonId : 919114
Franck Bonnetain
- Fonction : Auteur
- PersonId : 956767
Aimery de Gramont
- Fonction : Auteur
- PersonId : 761187
- ORCID : 0000-0001-7940-9877
Julien Taieb
- Fonction : Auteur
- PersonId : 756198
- ORCID : 0000-0002-9955-4753
Résumé
Purpose : Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers.
Methods : In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive.
Results : A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49).
Conclusion : IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.